A standard process of drug development can be roughly divided into three steps. A first step is, after investing medicinal needs and selecting a disease to be a target of the drug development, to search an effective substance for the disease, and discover (screen) an objective drug candidate. Subsequently, a second step is to verify the effectiveness and safety for the diagnosis and treatment of the disease targeted by the drug candidate through a nonclinical trial and a clinical trial, summarize its evaluation result in a new-drug application, and obtain its approval from a government. And, a third step is to sell the approved drug in a market to be used for medical care. In this drug-discovery process, as seen from a viewpoint such that a cost for its research and development is high, it has been reported that an amount equivalent to 30%, in some cases, 50% of a total research and development cost is spent on animal experiments.
Animal experiments are used in nonclinical trials, some clinical trials, or initial screening. Therefore, under a recent circumstance that a development cost per one item of the new drug almost reaches 100 billion yen, by developing an alternative low-cost test method instead of the animal experiments, a cost reduction effect in suppressing the research and development cost is expected. Further, also from a viewpoint of animal welfare and protection, particularly as seen from a recent trend in EU, reduction of the animal experiments has been already socially such a large stream that cannot be returned. Still further, it has been pointed out that an in vitro alternative method with using cells is advantageous for figuring out an action mechanism of in-vivo kinetics of a drug or a chemical compound, which is difficult to be understood by conventional animal experiments, more particularly, for evaluating metabolism, detoxification, and hepatic duct excretion in a liver, which is one of important indicators (in Non-patent Document 1).
Under such a background, approaches to alternative methods with using cells have been actively taken in the past. However, many methods have a limitation in the prediction of clinical reactions. A reason for this limitation has been considered that, in these culture methods, cells do not have a structure mimicking an actual in-vivo structure (in Non-patent Document 2). Therefore, the construction of a three-dimensional structure closer to a living body and the establishment of an in vitro assay system with using the structure have been required. More particularly, an in vitro assay system with using hepatocytes is highly expected, and an evaluation system for metabolism or bile canalicular excretion in a liver, which is one of important screening indicators, has been required. The bile canaliculus is a space bounded by two or more hepatocytes, and closes an intercellular space by a tight junction to prevent leakage of bile. The liver transports bile and metabolites from the hepatocytes into the bile canaliculi with using an ATP-dependent transporter expressed in a cell membrane. As a technique for measuring such a hepatic duct excretion, a sandwich method is cited (in Non-patent Document 3). However, practical use of the method showing a sufficient performance has not been achieved yet.
As a device for achieving the three-dimensional structure of the cell, a nanopillar cell culture sheet (hereinafter, referred to as a “nanopillar sheet” or a “NP sheet”) is cited (in Patent Document 1). The NP sheet is a scaffolding material for cell culture or tissue culture, which is produced by applying a microfabrication technology such as a nano-imprint technology. A feature of the nanopillar sheet is that, by using an artificially-designed fine three-dimensional structure as the scaffolding material, an effect as a device for three-dimensional culture can be expected. Some reports for the cell culture with using the nanopillar sheet have been made (in Patent Documents 2 and 3).    Patent Document 1: Japanese Patent Application Laid-Open Publication No. 2004-170935    Patent Document 2: Japanese Patent Application Laid-Open Publication No. 2006-223197    Patent Document 3: Japanese Patent Application Laid-Open Publication No. 2008-054566    Non-Patent Document 1: J. Cell Biol. 101: 914-923 (1985)    Non-Patent Document 2: J. Biomol. Screen. 9: 273-285 (2004)    Non-Patent Document 3: FASEB J 3: 174-177 (1989)